Medicine and Health Sciences Commons^™

The Oral Selective Estrogen Receptor Degrader Gdc-0810 (Arn-810) In Postmenopausal Women With Hormone Receptor-Positive Her2-Negative (Hr + /Her2 -) Advanced/Metastatic Breast Cancer, Aditya Bardia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

METHODS: A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

RESULTS: Patients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose …

Scaling-Up Child And Youth Mental Health Services: Assessing Coverage Of A County-Wide Prevention And Early Intervention Initiative During One Fiscal Year, Cole Hooley, Deborah Salvo, Derek S Brown, Lauren Brookman-Frazee, Anna S Lau, Ross C Brownson, Patrick J Fowler, Debbie Innes-Gomberg, Enola K Proctor

2020-Current year OA Pubs

PURPOSE: In the U.S., the percentage of youth in need of evidence-based mental health practices (EBPs) who receive them (i.e., coverage rate) is low. We know little about what influences coverage rates. In 2010, the Los Angeles County Department of Mental Health (LACDMH) launched a reimbursement-driven implementation of multiple EBPs in youth mental health care. This study examines two questions: (1) What was the coverage rate of EBPs delivered three years following initial implementation? (2) What factors are associated with the coverage rates?

METHODS: To assess coverage rates of publicly insured youth, we used LACDMH administrative claims data from July …

Sox9 Governs Gastric Mucous Neck Cell Identity And Is Required For Injury-Induced Metaplasia, Spencer G Willet, Nattapon Thanintorn, Helen Mcneill, Sung-Ho Huh, David M Ornitz, Won Jae Huh, Stella G Hoft, Richard J Dipaolo, Jason C Mills

2020-Current year OA Pubs

BACKGROUND & AIMS: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach.

METHODS: We used immunostaining …

Improvement In The Capacity For Activity Versus Improvement In Performance Of Activity In Daily Life During Outpatient Rehabilitation, Catherine E. Lang, Carey L. Holleran, Michael J. Strube, Terry D. Ellis, Caitlin A. Newman, Meghan Fahey, Tamara R. Deangelis, Timothy J. Nordahl, Darcy S. Reisman, Gammon M. Earhart, Keith R. Lohse, Marghuretta D. Bland

2020-Current year OA Pubs

UNLABELLED: We addressed questions about the potential discrepancy between improvements in activity capacity and improvements in activity performance in daily life. We asked whether this discrepancy is: 1. Common in routine, outpatient care, or an artifact of intervention studies? 2. Unique to upper limb (UL) rehabilitation, or is it seen in walking rehabilitation too? 3. Only seen in persons with stroke, or a broader neurorehabilitation problem?

METHODS:: A longitudinal, observational cohort of 156 participants with stroke or Parkinson disease (PD) receiving outpatient rehabilitation at 5 clinics was assessed around admission and monthly during their episode of care. Individual, longitudinal capacity …

Eliminating Central Line Associated Bloodstream Infections In Pediatric Oncology Patients: A Quality Improvement Effort, Daniel N. Willis, Karen Looper, Rema A. Malone, Barbara Ricken, Ashley Slater, Amanda Fuller, Meagan Mccaughey, Angela Niesen, Joan R. Smith, Beverly Brozanski

2020-Current year OA Pubs

UNLABELLED: Central Line-Associated Bloodstream Infections (CLABSI) are the largest contributor to harm across the Children's Hospital's Solutions for Patient Safety network. Pediatric hematology/oncology (PHO) patients are at increased risk for CLABSI due to multiple factors. Consequently, traditional CLABSI prevention strategies are insufficient to eliminate CLABSI in this high-risk population.

METHODS: Our SMART aim was to reduce the CLABSI rate by 50% from a baseline of 1.89/1000 central line days to less than 0.9/1000 central line days by December 31, 2021. We created a multidisciplinary team being mindful to identify roles and responsibilities upfront. We developed a key driver diagram and …

Case Report: Insulin Hypersensitivity In Youth With Type 1 Diabetes, Einas H Alkhatib, Jody B Grundman, Anna M Adamusiak, Melena D Bellin, Joel P Brooks, Kevin S Buckley, Erin M Janssen, Maleewan Kitcharoensakkul, Kyle P Mcnerney, Thea L Pfeifer, Brooke I Polk, Brynn E Marks

2020-Current year OA Pubs

OBJECTIVE: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).

METHODS: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.

RESULTS: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Symmetric Data-Driven Fusion Of Diffusion Tensor Mri: Age Differences In White Matter, Andrea Mendez Colmenares, Michelle B Hefner, Vince D Calhoun, Elizabeth A Salerno, Jason Fanning, Neha P Gothe, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of …

A Pilot Phase Ib Study To Evaluate Tadalafil To Overcome Immunosuppression During Chemoradiotherapy For Idh-Wild-Type Glioblastoma, Subhajit Ghosh, Tanner M Johanns, Milan G Chheda, Eric Liu, Omar Butt, Christopher Abraham, Shahed Badiyan, Yi Huang, David Denardo, Albert H Kim, Dennis Hallahan, Dinesh Thotala, Jiayi Huang

2020-Current year OA Pubs

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are critical regulators of immunosuppression and radioresistance in glioblastoma (GBM). The primary objective of this pilot phase Ib study was to validate the on-target effect of tadalafil on inhibiting MDSCs in peripheral blood and its safety when combined with chemoradiotherapy in GBM patients.

METHODS: Patients with newly diagnosed IDH-wild-type GBM received radiation therapy (RT) and temozolomide (TMZ) combined with oral tadalafil for 2 months. A historical cohort of 12 GBM patients treated with RT and TMZ was used as the comparison group. The ratio of MDSCs, T cells, and cytokines at week 6 of RT …

Transplantation Of Gut Microbiota From Old Mice Into Young Healthy Mice Reduces Lean Mass But Not Bone Mass, Lina Lawenius, Carrie Cowardin, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old …

Characterization Of Cerebrospinal Fluid (Csf) Microbiota At The Time Of Initial Surgical Intervention For Children With Hydrocephalus, Shailly Pandey, Kathryn B. Whitlock, Matthew R. Test, Paul Hodor, Christopher E. Pope, David D. Limbrick, Patrick J. Mcdonald, Jason S. Hauptman, Lucas R. Hoffman, Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in …

Patient Experiences With Thyroid Nodules: A Qualitative Interview Survey, Matthew R Naunheim, Manuela Von Sneidern, Molly N Huston, Okenwa C Okose, Amr H Abdelhamid Ahmed, Gregory W Randolph, Mark G Shrime

2020-Current year OA Pubs

OBJECTIVE: To qualitatively explore the broad set of preferences and attitudes patients have about thyroid nodules, which influence the decision-making process.

STUDY DESIGN: A descriptive survey design was administered as interviews.

SETTING: Outpatient thyroid surgery clinic.

METHODS: Semistructured interviews were conducted with 20 patients presenting for initial evaluation of thyroid nodules at a surgeon's office. Probative, open-ended questions were posed regarding diagnosis, treatment, risk attitudes, and the decision-making process. Thematic analysis was used to develop code-transcribed interviews, and an iterative refinement resulted in underlying themes.

RESULTS: During the diagnostic process, patients integrated emotional responses (fear, anxiety, and shock) with rationale …

Histopathological Evaluation Of Onchocerca Volvulus Nodules By Microscopy And By Digital Image Analysis For The Study Of Macrofilaricidal Drug Efficacy, Kerstin Fischer, Bettina Dubben, Linda B Debrah, Janina M Kuehlwein, Arcangelo Ricchiuto, Alexander Y Debrah, Achim Hoerauf, Gary J Weil, Peter U Fischer, Ute Klarmann-Schulz

2020-Current year OA Pubs

BACKGROUND: Novel drugs or drug combinations that kill or permanently sterilize adult

MATERIAL AND METHODS: Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously …

The Plasma Virome In Longitudinal Samples From Pregnant Patients, Molly J Stout, Anoop K Brar, Brandi N Herter, Ananda Rankin, Kristine M Wylie

2020-Current year OA Pubs

INTRODUCTION: Nucleic acid from viruses is common in peripheral blood, even in asymptomatic individuals. How physiologic changes of pregnancy impact host-virus dynamics for acute, chronic, and latent viral infections is not well described. Previously we found higher viral diversity in the vagina during pregnancy associated with preterm birth (PTB) and Black race. We hypothesized that higher diversity and viral copy numbers in the plasma would show similar trends.

METHODS: To test this hypothesis, we evaluated longitudinally collected plasma samples from 23 pregnant patients (11 term and 12 preterm) using metagenomic sequencing with ViroCap enrichment to enhance virus detection. Sequence data …

Conserved Gene Signatures Shared Among Mapt Mutations Reveal Defects In Calcium Signaling, Miguel A Minaya, Sidhartha Mahali, Abhirami K Iyer, Abdallah M Eteleeb, Rita Martinez, Guangming Huang, John Budde, Sally Temple, Alissa L Nana, William W Seeley, Salvatore Spina, Lea T Grinberg, Oscar Harari, Celeste M Karch

2020-Current year OA Pubs

No abstract provided.

The Vacc-Seqqc Project: Benchmarking Rna-Seq For Clinical Vaccine Studies, Johannes B Goll, Richard D Head, Et Al.

2020-Current year OA Pubs

[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].

Interactions Of Pathogenic Escherichia Coli With Ceacams, Alaullah Sheikh, James M Fleckenstein

2020-Current year OA Pubs

The pathogenic

Objective Response To Immune Checkpoint Inhibitor Therapy In Nras-Mutant Melanoma: A Systematic Review And Meta-Analysis, Zachary J Jaeger, Neel S Raval, Natalia K A Maverakis, David Y Chen, George Ansstas, Angela Hardi, Lynn A Cornelius

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We performed a comprehensive literature search across several large databases. Inclusion criteria were trials, cohorts, and large case series that analyzed the primary outcome of objective response rate by

RESULTS: Data on 1770 patients from ten articles were pooled for meta-analysis, and the objective response rate to ICIs was calculated to compare

DISCUSSION: In this meta-analysis evaluating the impact of

Oxidation Driven Reversal Of Pip2-Dependent Gating In Girk2 Channels, Sun-Joo Lee, Shoji Maeda, Jian Gao, Colin G Nichols

2020-Current year OA Pubs

Physiological activity of G protein gated inward rectifier K

Development Of An In-Vitro High-Throughput Screening System To Identify Modulators Of Genitalia Development, Yan Yin, Meade Haller, Tian Li, Liang Ma

2020-Current year OA Pubs

Sexually dimorphic outgrowth and differentiation of the embryonic genital tubercles (GTs) give rise to the penis in males and the clitoris in females. Defects in androgen production or in response to androgen signaling can lead to various congenital penile anomalies in both mice and humans. Due to lack of a high-throughput screening system, identification of crucial regulators of GT sexual differentiation has been slow. To overcome this research barrier, we isolated embryonic GT mesenchymal (GTme) cells to model genitalia growth and differentiation in vitro. Using either a mechanical or fluorescence-activated cell sorting-assisted purification method, GTme cells were isolated and assayed …

Intra-Articular Aav9 Α-L-Iduronidase Gene Replacement In The Canine Model Of Mucopolysaccharidosis Type I, Raymond Yu-Jeang Wang, Shih-Hsin Kan, Haoyue Zhang, Jodi D Smith, Afshin Aminian, Elizabeth Snella, Jackie K Jens, Sarah P Young, Patricia I Dickson, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type I (MPS I), an inherited lysosomal storage disorder characterized by deficiency of

Development Of A Goal Setting And Goal Management System: Intervention Mapping, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: Although goal setting and goal management (GSGM) is a key component of chronic disease management and rehabilitation practice, there is currently no widely used evidence-based intervention system available. This paper describes the theoretical underpinnings and development of a new intervention called MyGoals. MyGoals is designed to guide occupational therapy (OT) practitioners to implement theory-based, client-engaged GSGM for adults with chronic conditions in community-based OT rehabilitation settings.

METHODS: We first developed a planning team with two adults with chronic conditions, two clinicians, and two researchers. As a collaborative team, we co-developed MyGoals by following Intervention Mapping (IM) steps 1-4 and …

Situating Implementation Science (Is) In Res(Is)Tance: A Conceptual Frame Toward The Integration Of Scholarship From The Black Radical Tradition, Cory D Bradley, Whitney C Irie, Elvin H Geng

2020-Current year OA Pubs

This manuscript undertakes a disciplinary self-critique of the field of implementation science, a field which attempts to bridge the gap between evidence-based interventions and their practical application. Despite the heightened emphasis on health equity and racial disparities, the field's current discourse is limited by key epistemic shortcomings. First, even though prevalence of implementation gaps between racialized groups in the United States necessitates a comprehensive understanding of the systems perpetuating these disparities, the field does not operate with a general explanation for disparities not as a failure of systems, but a system historically and structural designed to produce disparities. Second, the …

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

Safety And Efficacy Of Mca‐M2 Thrombectomy In Delayed Time Window: A Propensity Score Analysis From The Star Registry, Kaustubh Limaye, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M. Willems, Ping An, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

Training, Supervision, And Experience Of Coaches Offering Digital Guided Self-Help For Mental Health Concerns, Ellen E Fitzsimmons-Craft, Elsa Rojas, Naira Topooco, Gavin N Rackoff, Nur Hani Zainal, Daniel Eisenberg, Jillian Shah, Christina Desage, Denise E Wilfley, Craig Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Machine Learning Pipelines Developed For The Prediction Of Cancelation Of Inappropriate Parathyroid Hormone-Related Peptide Orders Demonstrate Poor Performance In Predicting Provider Behavior, Nicholas C. Spies, Christopher W. Farnsworth, Ronald Jackups, Mark A. Zaydman

2020-Current year OA Pubs

No abstract provided.